Mammalian cells contain multiple DNA polymerizing activities. The functional relationship of these individual activities to cellular proliferation, differentiation and repair remains obscure. Preliminary studies have revealed that murine lymphoid tissues, particularly spleen, contain elevated Polymerase N activity when compared with non-lymphoid tissues. The activity of Polymerase N is greater in spleen than in regenerating liver at any time after partial hepatectomy. We propose to study in detail the identity, cell source and activation kinetics of individual DNA polymerases in lymphoid cell populations during proliferation and immunological activation in response to antigen. The proliferation of lymphoid cells occurs continually in normal animals and is accompanied by differentiation. This process can be accelerated and limited to a specific cell type in irradiated animals injected with thymus cells or bone marrow cells. Specific differentiation of individual cell populations in response to antigens will be compared with proliferation and differentiation in the absence of antigenic stimulation. The DNA polymerase activities of lymphoid cells in vivo will be compared with lymphocytes undergoing blastogenic transformation in vitro in response to mitogens. These studies will include a critical evaluation of the presence, characteristics and function of possible RNA-directed DNA polymerases ("reverse transcriptase") in murine lymphoid tissues.